1. Field of the Invention
The present invention relates to a method for preparing metal salts of valproic acid.
2. Description of Related Art
Valproic acid (VA), which is also known as 2-propylpentanoic acid, 2-propylvaleric acid or di-n-propylacetic acid, and its alkali/alkaline earth salts, e.g. sodium valproate, divalproex sodium and magnesium valproate, have been known to be active pharmaceutical ingredients for treatment of epileptic seizure, convulsion and migraine.
Various methods have been proposed to prepare metal salts of valproic acid. For example, U.S. Pat. Nos. 4,988,731 and 5,212,326 both disclose a process for the preparation of divalproex sodium (Depakote®). In these patents, divalproex sodium, an oligomeric 1:1 compound of valproic acid and sodium valproate, is prepared by dissolving valproic acid and sodium valproate in acetone at 50° C. followed by crystallization at 0° C. However, the disadvantage of the above process is the requirement of using organic solvents (e.g., acetone). Furthermore, the use of hygroscopic material of sodium valproate results in the operation of the process to be more complex. In addition, U.S. Pat. No. 6,753,349 discloses a method for producing valproic acid compounds that involves in the use of alkali metals carbonate/bicarbonate or alkaline earth metals carbonate/bicarbonate. However, it is understood that this process leads to the formation of CO2. Accordingly, the drawback of this patent is the dangerous risk in exhaustion of the undesirable CO2. Also, this additional operation complicates the process for producing valproic acid compounds.
Hence, there is still a need for a simple, safe and more efficient process for preparing metal salts of valproic acid.